Impact of plasma potassium normalization on short-term mortality in patients with hypertension and hypokalemia or low normal potassium

Abstract

Abstract Background Hypokalemia is common in patients treated with antihypertensive drugs, but the impact of correcting hypokalemia is insufficiently studied. We examined the consequences of hypokalemia and borderline hypokalemia correction in patients with hypertension. Methods We identified 8976 patients with hypertension and plasma potassium concentrations ≤3.7 mmol/L within 100 days from combination antihypertensive therapy initiation. The first measurement between 6 and 100 days after the episode with potassium ≤3.7 mmol/L was retained. We investigated all-cause and cardiovascular mortality within 60-days from the second potassium measurement using Cox regression. Mortality was examined for seven predefined potassium intervals derived from the second measurement: 1.5–2.9 mmol/L (n = 271), 3.0–3.4 mmol/L (n = 1341), 3.5–3.7 (n = 1982) mmol/L, 3.8–4.0 mmol/L (n = 2398, reference), 4.1–4.6 mmol/L (n = 2498), 4.7–5.0 mmol/L (n = 352) and 5.1–7.1 mmol/L (n = 134). Results Multivariable analysis showed that potassium concentrations 1.5–2.9 mmol/L, 3.0–3.4 mmol/L, 4.7–5.0 mmol/L and 5.1–7.1 mmol/L were associated with increased all-cause mortality (HR 2.39, 95% CI 1.66–3.43; HR 1.36, 95% CI 1.04–1.78; HR 2.36, 95% CI 1.68–3.30 and HR 2.62, 95% CI 1.73–3.98, respectively). Potassium levels <3.0 and > 4.6 mmol/L were associated with increased cardiovascular mortality. The adjusted standardized 60-day mortality risks in the seven strata were: 11.7% (95% CI 8.3–15.0%), 7.1% (95% CI 5.8–8.5%), 6.4% (95% CI 5.3–7.5%), 5.4% (4.5–6.3%), 6.3% (5.4–7.2%), 11.6% (95% CI 8.7–14.6%) and 12.6% (95% CI 8.2–16.9%), respectively. Conclusions Persistent hypokalemia was frequent and associated with increased all-cause and cardiovascular mortality. Increase in potassium to levels > 4.6 mmol/L in patients with initial hypokalemia or low normal potassium was associated with increased all-cause and cardiovascular mortality.